Since the ban of most chlorinated hydrocarbons as pesticides, the use of organophosphorus compounds has increased. While all organophosphorus insecticides inhibit acetylcholin-esterase, a few of these compounds cause delayed neurotoxicity. This was first demonstrated in man. Some species of experimental animals are susceptible (cats, dogs, cows and chickens) while others (rodents and some primates) are not. The test animal chosen to study delayed neurotoxicity is the adult chicken. The clinical condition becomes manifest first as ataxia followed by paralysis. Lesions are characterized by degeneration of axons with subsequent wallerian degeneration of myelin. Phenylphosphonothioate insecticides are generally suspected of being neurotoxic. EPN (O-ethyl O-4-nitrophenyl phenylphosphonothioate) produced delayed neurotoxicity in chickens and leptophos, another chemical which belongs to this group, has been implicated in poisoning and paralysis of some workers in the Texas factory where it was manufactured. The purpose of this study is to develop the cat as a practical animal model to study delayed neurotoxicity induced by organophosphorus compounds. We plan to carry on an integrated study to determine the following parameters after the dermal administration of a single dose or daily small doses of EPN to the cat: clinical condition, histopathological alterations in the nervous system, electrophysiological changes and biochemical parameters such as cholinesterases and acid phosphatases in the brain and plasma and neurotoxic esterase in the brain. These results will be correlated with the metabolic and pharmacokinetic studies of a single or daily doses of 14C-EPN applied dermally.